Note: this is one of two SNPs within the TCF7L2 gene that have been reported to be associated with type-2 diabetes, the other being rs4506565. They have approximately equal power to estimate risk for type-2 diabetes, and the results from one correlate 92% of the time with the other. [PMID 17554300]

This SNP is one of 4 relatively common SNPs reported to represent risk for type-2 diabetes in the DESIR prospective study of 3,877 Caucasian participants. Under an additive model, the odds ratio for the (T) risk allele is 1.45 (CI: 1.2-1.77, p=0.0002). For the 4 SNPs, each risk allele increased type-2 diabetes risk by 1.34x (p=2x10e-6), with an odds ratio of 2.48 (CI: 1.59-3.86) for carriers of 4 or more compared to those with one or none (risk alleles).[PMID 17977958]

Contrary to what's been seen in most populations studied so far, the association between rs7903146 and type-2 diabetes apparently does not hold in Arab populations, based on a case-control study of 522 Saudi patients and 346 controls.[PMID 18655717]

A HuGE review and meta-analysis including over 35,000 type-2 diabetes cases and 39,000 controls concluded that the Bayesian odds ratio for rs7903146(T;T) homozygotes and (C;T) heterozygotes versus (C;C) homozygotes was 1.968 (95% credible interval (CrI): 1.790 - 2.157) and 1.406 (95% CrI: 1.341 - 1.476), respectively, and the population attributable risk (PAR) for the (C;T)/(T;T) genotypes of this variant is 16.9% overall. Along with 3 other TCF7L2 SNPs, a multiplicative genetic model was indicated.[PMID 19228405]

A study of over 13,000 individuals initially free of cancer and followed over 10+ years found that the rs7903146(T) allele was associated with increased risk of colorectal cancer, with an adjusted odds ratio of 1.25 (CI:0.85-1.83) and 2.15 (CI:1.27-3.64) for the (C;T) and (T;T) genotypes, respectively.[PMID 18268068]

Does the association with type 2 diabetes hold for youth as well as for adults? Among African American youth, each copy of a rs7903146(T) allele was associated with a 1.97-fold (CI:1.37 - 2.82) increased odds for type 2 diabetes (p?<?0.0001), yet no significant association was detected in non-Hispanic white youth (adjusted odds ratio 1.14; CI: 0.73 - 1.79).[PMID 21109996]

[PMID 19258437] A Genetic Variant in the IGF2BP2 Gene may Interact with Fetal Malnutrition on Glucose Metabolism.

[PMID 18555673] The effect of WNT5B IVS3C>G on the susceptibility to type 2 diabetes in UK Caucasian subjects

[PMID 20682688] Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: common genetic variants in GCK and TCF7L2 are associated with fasting and post-challenge glucose levels in pregnancy and with the new consensus definition of gestational diabetes from the International Association of Diabetes and Pregnancy Study Groups

[PMID 21678030] Association of a common variant in TCF7L2 gene with type 2 diabetes mellitus in a Persian population

[PMID 22052079] Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs

[PMID 22109281] The type 2 diabetes-associated variant in TCF7L2 is associated with latent autoimmune diabetes in adult Europeans and the gene effect is modified by obesity: a meta-analysis and an individual study

[PMID 16936218] Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish: replication and evidence for a role in both insulin secretion and insulin resistance.

[PMID 17003358] Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals.

[PMID 23926018] [Study of the association between SNP rs7903146(C/T) in TCF7L2 and metabolic syndrome in Chinese Korean and Han populations from Yanbian]

[PMID 23942764] Parental history of type 2 diabetes, TCF7L2 variant and lower insulin secretion are associated with incident hypertension. Data from the DESIR and RISC cohorts

[PMID 23942586] Mediterranean Diet Reduces the Adverse Effect of the TCF7L2-rs7903146 Polymorphism on Cardiovascular Risk Factors and Stroke Incidence: A randomized controlled trial in a high-cardiovascular-risk population

[PMID 27650258] A multianalytical approach to evaluate the association of 55 SNPs in 28 genes with obesity risk in North Indian adults.

[PMID 28072873] Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development.

[PMID 28101933] Associations of common variants in the SLC16A11, TCF7L2, and ABCA1 genes with pediatric-onset type 2 diabetes and related glycemic traits in families: A case-control and case-parent trio study.